Neuropathological characterization of mutant amyloid precursor protein yeast artificial chromosome transgenic mice

Laura Shapiro Kulnane, Bruce Lamb

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Mutations in the amyloid precursor protein (APP) gene result in elevated production and deposition of the 42 amino acid β-myloid (Aβ1-42) peptide and early-onset Alzheimer's disease (AD). To accurately examine the effect of the APP FAD mutations in vivo, we introduced yeast artificial chromosomes (YACs) containing the entire genomic copy of human APP harboring FAD mutations into transgenic mice. Our current results demonstrate that mutant APP YAC transgenic mice exhibit many features characteristic of human AD, including regional deposition of Aβ with preferential deposition of Aβ1-42, extensive neuritic abnormalities as evidenced by staining with APP, ubiquitin, neurofilament, and hyperphosphorylated tau antibodies, increased markers of inflammation, and the overlapping deposition of Aβ with apolipoproteins E and J. Our results also suggest that APP YAC transgenic mice possess unique pathological attributes when compared to other transgenic mouse models of AD that may reflect the experimental design of each model.

Original languageEnglish (US)
Pages (from-to)982-992
Number of pages11
JournalNeurobiology of Disease
Volume8
Issue number6
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Yeast Artificial Chromosomes
Amyloid beta-Protein Precursor
Mutant Proteins
Amyloid
Transgenic Mice
Alzheimer Disease
Flavin-Adenine Dinucleotide
Mutation
Clusterin
Intermediate Filaments
Apolipoproteins E
Ubiquitin
Research Design
Staining and Labeling
Inflammation
Amino Acids
Peptides
Antibodies
Genes

ASJC Scopus subject areas

  • Neurology

Cite this

Neuropathological characterization of mutant amyloid precursor protein yeast artificial chromosome transgenic mice. / Kulnane, Laura Shapiro; Lamb, Bruce.

In: Neurobiology of Disease, Vol. 8, No. 6, 2001, p. 982-992.

Research output: Contribution to journalArticle

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